This application is a request for an ADAMHA RSDA (Level II). The long-term goal of this project is to determine if fetal exposure to ethanol leads to immune impairment, and if so, the nature and extent of the immune deficiency. The approach uses female mice fed a liquid diet containing ethanol at various doses. Offspring of these mothers will be compared to offspring of ad lib and pair-fed controls. Mice at various ages from late fetal to 8-week old, (depending on the specific test) will be subjected to a variety of in vitro and in vivo immunological tests to assess competence of T cells, B cells, natural killer cells and phagocytic cells. If immune defects are found, further experimentation will be done to pinpoint the critical period of fetal development and minimum dose for alcohol-induced damage. Another question to be addressed is whether severity of immune dysfunction correlates with "classical" fetal alcohol syndrome anomalies such as cranio-facial and brain defects. Offspring of alcohol-fed mother will be testes several weeks after birth as well as in the late fetal or neonatal period to determine how long-lasting immune deficiencies are. Mice of inbred strains which differ in activity of alcohol- metabolizing enzymes, will be used to study the role of genetics in susceptibility to immune deficiency caused by maternal alcoholism. If this study demonstrates a high incidence of immune deficiency as a result of maternal alcohol consumption, there are obvious health-related implications. This study should increase our over- all understanding of risk to the fetus from maternal alcoholism. In addition, a correlation between classical fetal alcohol syndrome features and immune deficiency in experimental animals might alert the medical community to the advisability of examining FAS patients for immune deficiency as well as other currently recognized health risks associated with the syndrome. Plans for professional growth include acquiring skills and knowledge in what is for me a new field (alcohol as a teratogen), and combining this interest with my long-standing involvement in immunology. More specifically, I plan to 1) develop in my own laboratory the methods used in alcohol teratogenesis work; 2) attend scientific meetings in the area of alcohol research, as well as immunology; 3) if possible, consult with a human geneticist who sees a rather large number of patients with FAS in the course of his clinical practice.